POS0524 CXCL12 AND CXCR4 AS NOVEL BIOMARKERS IN PATIENTS WITH GOUTY ARTHRITIS
Authors: S. K. Kim, J. Y. Choe, H. Lee, J. W. Kim
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> CXCR4 binds to its ligand CXC chemokine CXCL12 and plays a role in induction of recruitment of inflammatory cells including leukocytes and endothelial cells. The CXCL12/CXCR4 axis has been implicated in the pathogenesis of some types of inflammatory arthritis and autoimmune diseases including rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis. Evidence of the pathogenic role of CXCR4 and CXCL12 in uric acid-induced inflammation has not been presented. <h3>Objectives</h3> The aim of this study is to evaluate the expression of chemokine receptor CXCR4 and its ligand CXCL12 in patients with gout and uric acid-induced inflammation. <h3>Methods</h3> Forty patients with intercritical gout and 27 controls were consecutively enrolled. Serum levels of interleukin-1β (IL-1β, IL-18, CXCL12, and CXCR4 were assessed using enzyme-linked immunosorbent assay. Gene and protein expression for these target molecules was measured in human U937 cells incubated with monosodium urate (MSU) crystals using real-time reverse transcription polymerase chain reaction and Western blot analysis. <h3>Results</h3> Patients with intercritical gout showed higher serum IL-1β, IL-18, and CXCL12 levels than those in controls, but not serum CXCR4 level. Serum CXCR4 level in gout patients was associated with serum IL-18 level, uric acid level, and uric acid/creatinine ratio (r = 0.331, p = 0.037; r = 0.346, p = 0.028; r = 0.361, p = 0.022, respectively). U937 cells treated with MSU crystals significantly induced CXCL12 and CXCR4 mRNA and protein expression, in addition to IL-1β and IL-18. In cells transfected with IL-1β siRNA or IL-18 siRNA, CXCL12 and CXCR4 expression was downregulated compared to non-transfected cells in MSU crystal-induced inflammation. Receiver operator characteristic (ROC) curve analysis showed that serum CXCL12 for the diagnosis of gout was an area under roc curve (AUC) of 0.690 (p = 0.009). <h3>Conclusion</h3> This study reveals that CXCL12 and CXCR4 are involved in the pathogenesis of uric acid-induced inflammation and gouty arthritis. <h3>References</h3> [1]BIANCHI ME, MEZZAPELLE R: The Chemokine Receptor CXCR4 in Cell Proliferation and Tissue Regeneration. Front Immunol 2020; 11: 2109. [2]GARCÍA-CUESTA EM, SANTIAGO CA, VALLEJO-DÍAZ J, JUARRANZ Y, RODRÍGUEZ-FRADE JM, MELLADO M: The Role of the CXCL12/CXCR4/ACKR3 Axis in Autoimmune Diseases. Front Endocrinol (Lausanne) 2019; 10: 585. [3]JANSSENS R, STRUYF S, PROOST P: The unique structural and functional features of CXCL12. Cell Mol Immunol 2018; 15(4): 299-311. [4]DE KLERCK B, GEBOES L, HATSE S et al.: Pro-inflammatory properties of stromal cell-derived factor-1 (CXCL12) in collagen-induced arthritis. Arthritis Res Ther 2005; 7(6): R1208-20. [5]PENG L, ZHU N, MAO J et al.: Expression levels of CXCR4 and CXCL12 in patients with rheumatoid arthritis and its correlation with disease activity. Exp Ther Med 2020; 20(3): 1925-34. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.